Apatinib
Rivoceranib, also known as apatinib, is a tyrosine kinase inhibitor that selectively inhibits the vascular endothelial growth factor receptor-2. It is an orally bioavailable, small molecule agent which is thought to inhibit angiogenesis in cancer cells; specifically, rivoceranib inhibits VEGF-mediated endothelial cell migration and proliferation thus blocking new blood vessel formation in tumor tissue. This agent also mildly inhibits c-Kit and c-SRC tyrosine kinases.
Apatinib was first synthesized by Advenchen Laboratories in California, US and licensed out global rights to HLB in 2020, and is being developed by Jiangsu Hengrui Medicine, LSK BioPartners and HLB Life Science. It is an investigational cancer drug undergoing clinical trials as a potential targeted treatment for metastatic gastric carcinoma, metastatic breast cancer, adenoid cystic carcinoma, and advanced hepatocellular carcinoma.
Phase I/II clinical study
The principal investigator from Fudan University, China, presented results of phase I/II human clinical studies at the 2009 CSCO Meeting. Cancer patients were administered varied doses of apatinib daily for 28 days. Apatinib was well tolerated at doses below 750 mg/day, 3 of 3 dose-limiting toxicities were reported at 1000 mg/day and the maximum tolerated dose is determined to be 850 mg/day. The investigator also reported of 65 cancer patients treated in phase I/II, 1.54% had a complete response, 12.31% had a partial response, 66.15% had stable disease and 20% had progressive disease.A separate published report on the safety and pharmacokinetics of apatinib in Human clinical studies concludes that it has encouraging antitumor activity across a broad range of cancer types.
Status
There is a phase II/III study recruiting patients in China to determine whether apatinib can improve progression-free survival compared with placebo in patients with metastatic gastric carcinoma who have failed two lines of chemotherapy. Apatinib was approved by CFDA in December, 2014 for patients with late-stage gastric carcinoma in China. A phase IV study on safety of Apatinib started in April, 2015. The study aims to recruit 2,000 patients.As of November 2010, two additional phase II clinical studies have been initiated for apatinib in metastatic triple-negative breast cancer patients and advanced hepatocellular carcinoma.
In March 2011, Bukwang announced that it filed an IND to the Korean FDA to begin Human clinical studies of apatinib in phase II.
In August 2018, Bukwang licensed out the commercial rights in Korea for rivoceranib to HLB Life Science Medicare.